Evaluation of Rituximab for Induction and Maintenance Therapy in Patients 75 Years and Older With Antineutrophil Cytoplasmic Antibody–Associated Vasculitis
Authors: Sara Thietart, Alexandre Karras, Jean-François Augusto, Carole Philipponnet, Pierre-Louis Carron, Xavier Delbrel, Rafik Mesbah, Gilles Blaison, Pierre Duffau, Khalil El Karoui, Perrine Smets, Jonathan London, Luc Mouthon, Loïc Guillevin, Benjamin Terrier, Xavier Puéchal, Asma Alla, Vincent Audard, Olivier Aumaître, Stéphane Bally, Bernard Bonnotte, Pierre Charles, Pascal Cohen, Alice Corbel, Maud Cousin, Yoann Cabrol, Stéphane Durupt, Benoit Faucher, Ségolène Gendreau, Nicolas Girszyn, Pascal Godmer, Mohamed Hamidou, Noémie Jourde-Chiche, Adeline Lacraz, Cédric Landron, Claire Le Jeunne, François Lifermann, Eric Liozon, Sylvain Marchand-Adam, François Maurier, Arsène Mékinian, Christian Pagnoux, Thomas Quéméneur, Viviane Queyrel, Hanta Nirina Rakotoarivelo, Alexis Régent, Quitterie Reynaud, Virginie Rieu, Karim Sacre, André Soto, Dimitri Titeca-Beauport, Stéphane Vinzio
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Older patients are underrepresented in studies of rituximab for the treatment of antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis. Little is known about outcomes and adverse events associated with the use of rituximab therapy among patients 75 years and older with ANCA-associated vasculitis. <h3>Objective</h3> To examine outcomes and adverse events associated with the use of rituximab therapy in patients 75 years and older with ANCA-associated vasculitis, specifically granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA). <h3>Design, Setting, and Participants</h3> This multicenter cohort study involved 93 patients 75 years and older with ANCA-associated vasculitis from 36 university and nonuniversity hospitals in France. Data were obtained from the French Vasculitis Study Group database between January 1, 2000, and July 1, 2018, and a call for observation sent to French Vasculitis Study Group members on June 6, 2019. Data analysis was performed from November 15 to December 31, 2021. Inclusion criteria included a diagnosis of GPA or MPA according to European Medicines Agency classification criteria and receipt of treatment with rituximab after age 75 years. Patients were excluded if they were missing relevant clinical or biological data. Data on race and ethnicity were not reported because inclusion of this information was not authorized by the ethics committee. <h3>Exposure</h3> At least 1 infusion of rituximab as induction or maintenance therapy. <h3>Main Outcomes and Measures</h3> Occurrence of remission, relapse, drug discontinuation, death, and serious infections (including types of serious infections). <h3>Results</h3> Of 238 patients screened, 93 were included (median [IQR] age, 79.4 [76.7-83.1] years; 51 women [54.8%]); 52 patients (55.9%) had a diagnosis of GPA, and 41 (44.1%) had a diagnosis of MPA. Thirty patients (32.3%) received rituximab as induction therapy in combination with high-dose glucocorticoid regimens, 27 (29.0%) received rituximab as maintenance therapy, and 36 (38.7%) received rituximab as both induction and maintenance therapy. The median (IQR) follow-up was 2.3 (1.1-4.0) years. Among 66 patients who received rituximab as induction therapy, 57 (86.4%) achieved remission, and 2 (3.0%) experienced relapses. The incidence of serious infection was significantly higher when rituximab was used as induction therapy vs maintenance therapy (46.6 [95% CI, 24.8-79.7] per 100 patient-years vs 8.4 [95% CI, 3.8-15.9] per 100 patient-years;<i>P</i> = .004). Most infections (12 of 22 [54.5%]) were gram-negative bacterial infections. The incidence of death was 19.7 (95% CI, 7.2-42.9) per 100 patient-years among those who received rituximab as induction therapy and 5.3 (95% CI, 1.9-11.6) per 100 patient-years among those who received rituximab as maintenance therapy. <h3>Conclusions and Relevance</h3> In this cohort study, rituximab therapy was associated with achievement and maintenance of remission in most patients 75 years and older with ANCA-associated vasculitis. The incidence of serious infections and death was high when rituximab was used as induction therapy in combination with high-dose glucocorticoid regimens but not when rituximab was used as maintenance therapy. Efforts might focus on reducing serious infections during the first months of therapy.